Background/Purpose: Positron emission tomography (PET) is useful to demonstrate fluorodeoxyglucose (FDG) uptake in the large arteries in both Takayasu’s arteritis (TAK) and giant cell arteritis (GCA). Delayed FDG-PET imaging at 2 hours rather than 1 hour after FDG injection has greater sensitivity to detect vascular wall inflammation as measured by FDG uptake.  The specific cell populations responsible for FDG uptake within the large arteries are not well defined. The objective of this study was to assess whether vascular PET activity is associated with specific leukocyte subsets in peripheral blood at 1- and 2-hour post-FDG injection timepoints in patients with TAK and GCA.

Methods: Patients with TAK and GCA were recruited into a prospective, observational cohort.  All patients received PET imaging 2 hours after FDG injection, and a random subset of these patients had additional PET imaging 1 hour after FDG injection.  PETVAS, a qualitative summary score of arterial uptake in 9 arterial territories, was used to quantify vascular PET activity.  Absolute neutrophil, monocyte, and lymphocyte counts were determined by complete blood counts.  CD8+ and CD4+ T lymphocytes, and CD19+ B lymphocytes were quantified by flow cytometry.  CRP and ESR were measured.  All laboratory tests were performed within 24 hours of PET imaging.  Mixed model linear regression was used to identify associations between PETVAS and leukocyte populations, ESR, and CRP at both timepoints, adjusting for daily prednisone dose.

Results: 91 patients (TAK = 38, GCA = 53) contributed 201 visits for the 2-hour imaging timepoint.  A subset of 75 patients (TAK = 31, GCA = 44) contributed 158 visits for the 1-hour imaging timepoint.  Baseline characteristics were as follows: female gender (TAK: 79%, GCA: 75%), average age (TAK: 36.1±11 years, GCA: 70±8 years), average prednisone dose (TAK: 3.8±6 mg/day, GCA: 14.3±19 mg/day), ESR (TAK: 20.8±11 mm/hr, GCA: 25.3±24 mm/hr), and CRP (TAK: 10.6±12 mg/L, GCA: 10.2±21 mg/L).

At the 2-hour time point, PET activity was associated with absolute monocyte count in TAK (β estimate: 1.47, 95%CI: 1.04-2.08) and GCA (β estimate: 1.20, 95%CI: 1.02-1.42).  PET activity at the 2-hour timepoint was not associated with other leukocyte populations.  At the 1-hour timepoint, CD8+ T lymphocyte count was weakly associated with PET activity in patients with TAK (β estimate: 1+4.6e^-4, 95%CI: 1+3.1e^-6 – 1+9.0e^-4) but not in patients with GCA (β estimate: 1.00, 95%CI: 0.99-1.02).  Other leukocyte populations, including absolute monocyte count, were not associated with PET activity at the 1-hour timepoint.  There was no association between CRP or ESR with PET activity in TAK or GCA at either timepoint.

Conclusion: In both TAK and GCA, delayed FDG-PET imaging is associated with a patient’s absolute monocyte count.  The monocyte/macrophage lineage likely contributes to FDG uptake in large-vessel vasculitis and could be an important cell population to target therapeutically in these diseases.  Circulating biomarkers related to monocytes may constitute novel biomarkers for vascular PET activity.  Future studies that compare circulating biomarkers to vascular PET activity should employ delayed imaging approaches.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-leukocyte-populations-in-peripheral-blood-and-arterial-wall-inflammation-assessed-by-fdg-pet-in-takayasus-arteritis-and-giant-cell-arteritis/